The purpose of this proposal is to analyze pancreatic secretions from normal subjects, patients with suspected or established pancreatic disease including pancreatitis and cancer of the pancreas in order to detect specific components or characteristic protein profiles which may facilitate early detection of cancer of the pancreas or help in the differential diagnosis of this malignancy. Because of the extreme difficulties in obtaining pancreatic fluid from patients with cancer of the pancreas, a second purpose of the proposed research is to monitor corresponding pancreatic secretory proteins in hamsters during induction of pancreatic neoplasms and to seek correlations of the results with analogous observations made in patients with suspected or diagnosed carcinoma of the pancreas. In preceding research we have shown that several parameters exhibit statistically significant changes during pancreatic disease. For instance the ratio of cationic/anionic trypsinogen appears to be a highly critical indicator of pancreatic pathology even at a time when clinical symptoms are not yet evident. We propose to extend this approach to other enzymes, in particular RNase and DNase and to continue this research in conjunction with animal models during induction of pancreatic tumors in order to determine the earliest possible time during carcinogenesis that changes of such parameters can be detected. Sensitive methods for the measurement of these enzymes and proteins have been established in our laboratories and others will be developed in the course of the proposed work. Human pancreatic fluid will be collected by pancreatic ductal cannulation of healthy volunteers and patients scheduled for diagnosis by endoscopic retrograde cholangiopancreatography.